eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs
Thyroid, Medullary Carcinoma
Updated: Apr 18, 2006
Introduction
Background
Medullary carcinoma of the thyroid (MTC) is a distinct thyroid carcinoma that originates in the parafollicular C cells of the thyroid gland. These C cells produce calcitonin.
MTC has a genetic association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but it has an inheritable non-MEN mode of transmission.
Sporadic, or isolated, MTC occurs in 75% of patients, and familial MTC comprises the rest.
Outcome depends on extent of disease, nature of tumor biology, and overall efficacy of surgical treatment.
Advances in genetic testing in the past few years have revolutionized the management of this disease.
Pathophysiology
MTC is usually diagnosed on physical examination as a solitary neck nodule, and early spread to regional lymph nodes is common. Distant metastases occur in the liver, lung, bone, and brain.
Sporadic MTC usually is unilateral. In association with MEN syndromes, it always is bilateral and multicentric. MTC typically is the first abnormality observed in both MEN 2A and 2B syndromes.
In addition to producing calcitonin, MTC cells can produce several other hormones, including corticotropin, serotonin, melanin, and prostaglandins; moreover, paraneoplastic syndromes (eg, carcinoid syndrome, Cushing syndrome) can occur in these patients.
Mutations in the ret protooncogene, a receptor protein tyrosine kinase encoded on chromosome 10, have been recently classified into discrete subtypes; prophylactic thyroidectomy can now be offered to specific types of patients with this genetic abnormality.
Frequency
United States
MTC comprises less than 10% of all thyroid cancers. This figure translates into approximately 1000 diagnoses per year.
International
International incidence is similar to that in the United States.
Mortality/Morbidity
Isolated MTC typically demonstrates a relatively indolent biologic progression. While regional lymph node metastases are possible, the lesion may not spread outside of the cervical region until several months later. MTC associated with MEN syndromes may have a more aggressive course, which also depends on associated comorbidity (eg, pheochromocytoma).
Interestingly, despite advances in genetic screening for the ret protooncogene, recent evidence has yet to show a definitive impact on disease prognosis in preliminary population studies.
Age
Peak incidence of isolated MTC occurs in the fifth or sixth decade of life, and peak incidence of MTC associated with MEN 2A or 2B occurs during the second or third decade of life.
Clinical
History
A specific constellation of symptoms of medullary thyroid carcinoma (MTC) is not usually noted; however, one or more of the following symptoms may be observed:
- Patients may describe a lump at the base of the neck, which may interfere with or become more prominent during swallowing.
- Patients with locally advanced disease may present with hoarseness, dysphagia, and respiratory difficulty.
- Although uncommon, patients may present with various paraneoplastic syndromes, including Cushing or carcinoid syndrome.
- Diarrhea may occur from increased intestinal electrolyte secretion secondary to high plasma calcitonin levels.
- Distant metastases (eg, lung, liver, bone) may produce symptoms of weight loss, lethargy, and bone pain.
Physical
- Physical examination may demonstrate a dominant thyroid nodule at the base of the neck.
- Palpable cervical lymphadenopathy signifies disease that has progressed locally.
- Abdominal pain, jaundice, and rarely, bone tenderness may occur in patients with systemic metastases.
Causes
- MTC has a genetic association with MEN syndromes types 2A and 2B; however, it is inheritable by a non-MEN mode of transmission. Sporadic MTC occurs in 75% of patients, and familial MTC comprises the rest.
- Ret has led to MTC development in cells derived from neural crest tissue.
More on Thyroid, Medullary Carcinoma |
 Overview: Thyroid, Medullary Carcinoma |
| Differential Diagnoses & Workup: Thyroid, Medullary Carcinoma |
| Treatment & Medication: Thyroid, Medullary Carcinoma |
| Follow-up: Thyroid, Medullary Carcinoma |
| References |
| Next Page » |
References
Carlomagno F, Santoro M. Identification of RET kinase inhibitors as potential new treatment for sporadic and inherited thyroid cancer. J Chemother. Nov 2004;16 Suppl 4:49-51. [Medline].
Chi DD, Moley JF. Medullary thyroid carcinoma: genetic advances, treatment recommendations, and the approach to the patient with persistent hypercalcitoninemia. Surg Oncol Clin N Am. Oct 1998;7(4):681-706. [Medline].
Evans DB, Fleming JB, Lee JE, et al. The surgical treatment of medullary thyroid carcinoma. Semin Surg Oncol. 1999;16:50-63. [Medline].
Fitze G. Management of patients with hereditary medullary thyroid carcinoma. Eur J Pediatr Surg. Dec 2004;14(6):375-83. [Medline].
Gibelin H, Essique D, Jones C, et al. Increased calcitonin level in thyroid nodules without medullary carcinoma. Br J Surg. May 2005;92(5):574-8. [Medline].
Hyer SL, Newbold K, Harmer C. Familial medullary thyroid cancer: clinical aspects and prognosis. Eur J Surg Oncol. May 2005;31(4):415-9. [Medline].
Kebebew E, Greenspan FS, Clark OH, et al. Extent of disease and practice patterns for medullary thyroid cancer. J Am Coll Surg. Jun 2005;200(6):890-6. [Medline].
Moley JF. Medullary thyroid cancer. Surg Clin North Am. 1995;75:405-20.
Quayle FJ, Moley JF. Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes. J Surg Oncol. Mar 1 2005;89(3):122-9. [Medline].
Rosenthal MS, Pierce HH. Inherited medullary thyroid cancer and the duty to warn: revisiting Pate v. Threlkel in light of HIPAA. Thyroid. Feb 2005;15(2):140-5. [Medline].
Shaha AR. Management of the neck in thyroid cancer. Otolaryngol Clin North Am. 1998;31:823-31.
Udelsman R, Lakatos E, Ladenson P. Optimal surgery for papillary thyroid carcinoma. World J Surg. 1996;20:88-93. [Medline].
Further Reading
Keywords
medullary thyroid carcinoma, MTC, thyroid cancer, thyroid tumor, multiple endocrine neoplasia, MEN, thyroidectomy, hypothyroidism
